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Mäkinen, V.

Publications and source records attributed to Mäkinen, V..

4 recordsLinked to original sources

GraphChainer: Co-linear Chaining for Accurate Alignment of Long Reads to Variation Graphs

Aligning reads to a variation graph is a standard task in pangenomics, with downstream applications such as improving variant calling. While the vg toolkit (Garrison et al., Nature Biotechnology, 2018) is a popular aligner of short reads, GraphAligner (Rautiainen and Marschall, Genome Biology, 2020) is the state-of-the-art aligner of erroneous long reads. GraphAligner works by finding candidate read occurrences based on individually extending the best seeds of the read in the variation graph. However, a more principled approach recognized in the community is to co-linearly chain multiple seeds. We present a new algorithm to co-linearly chain a set of seeds in a string labeled acyclic graph, together with the first efficient implementation of such a co-linear chaining algorithm into a new aligner of erroneous long reads to acyclic variation graphs, GraphChainer. Compared to GraphAligner, GraphChainer aligns 12% to 17% more reads, and 21% to 28% more total read length, on real PacBio reads from human chromosomes 1, 22 and the whole human pangenome. On both simulated and real data, GraphChainer aligns between 95% and 99% of all reads, and of total read length. We also show that minigraph (Li et al., Genome Biology, 2020) and minichain (Chandra and Jain, RECOMB, 2023) obtain an accuracy of less than 60% on this setting. GraphChainer is freely available at https://github.com/algbio/GraphChainer. The datasets and evaluation pipeline can be reached from the previous address.

bioinformatics↗

Genomic Epidemiology with Mixed Samples

Genomic epidemiology is a tool for tracing transmission of pathogens based on whole-genome sequencing. We introduce the mGEMS pipeline for genomic epidemiology with plate sweeps representing mixed samples of a target pathogen, skipping the colony pick step. The pipeline includes the novel mGEMS read binner for probabilistic assignments of sequencing reads, and the scalable pseudoaligner Themisto. We demonstrate the effectiveness of our approach using closely related samples in a nosocomial setting, obtaining results that are comparable to those based on colony picks. Our results lend firm support to more widespread consideration of genomic epidemiology with mixed infection samples.

bioinformatics↗

Bit-parallel sequence-to-graph alignment

Graphs are commonly used to represent sets of sequences. Either edges or nodes can be labeled by sequences, so that each path in the graph spells a concatenated sequence. Examples include graphs to represent genome assemblies, such as string graphs and de Bruijn graphs, and graphs to represent a pan-genome and hence the genetic variation present in a population. Being able to align sequencing reads to such graphs is a key step for many analyses and its applications include genome assembly, read error correction, and variant calling with respect to a variation graph. Here, we generalize two linear sequence-to-sequence algorithms to graphs: the Shift-And algorithm for exact matching and Myers bitvector algorithm for semi-global alignment. These linear algorithms are both based on processing w sequence characters with a constant number of operations, where w is the word size of the machine (commonly 64), and achieve a speedup of w over naive algorithms. Our bitvector-based graph alignment algorithm reaches a worst case runtime of [Formula] for acyclic graphs and O(V + mE log w) for arbitrary cyclic graphs. We apply it to four different types of graphs and observe a speedup between 3.1-fold and 10.1-fold compared to previous algorithms.

bioinformatics↗

CHIC: a short read aligner for pan-genomic references

Recently the topic of computational pan-genomics has gained increasing attention, and particularly the problem of moving from a single-reference paradigm to a pan-genomic one. Perhaps the simplest way to represent a pan-genome is to represent it as a set of sequences. While indexing highly repetitive collections has been intensively studied in the computer science community, the research has focused on efficient indexing and exact pattern patching, making most solutions not yet suitable to be used in bioinformatic analysis pipelines.\n\nResultsWe present CHIC, a short-read aligner that indexes very large and repetitive references using a hybrid technique that combines Lempel-Ziv compression with Burrows-Wheeler read aligners.\n\nAvailabilityOur tool is open source and available online at https://gitlab.com/dvalenzu/CHIC

bioinformatics↗